To compare the safety and efficacy of rectal diazepam and buccal midazolam for the treatment of acute tonic-clonic seizures in children, researchers in the United Kingdom conducted a multicenter, nonblinded, randomized controlled trial. The study group included 177 patients, ages 6 months and older, representing 219 separate emergency department visits to 1 of 4 participating hospitals. Participants’ median age was 3 years (range: age 7 months to 15 years) and 98 of the 177 (55%) were male. All had visible seizure activity upon arrival in the ED, and none had established intravenous access. The dose of midazolam or diazepam was approximately 0.5 mg/kg based on estimated weight. The intravenous preparation of midazolam was dripped into the buccal cavity between the gum and cheeks using a needle or straw. Of the 219 episodes, 109 received buccal midazolam and 110 received rectal diazepam. In 68 episodes (31%), a prehospital emergency treatment (67 rectal diazepam, 1 rectal paraldehyde) had been administered; 35 of these children subsequently were treated with buccal midazolam and 33 with rectal diazepam.
Therapeutic success was defined as the cessation of clinical seizure activity within 10 minutes of administration without respiratory depression requiring assisted breathing and without further seizure activity within 1 hour. Therapeutic success was achieved in 56% (61 of 109) of the buccal midazolam group and in 27% (30 of 110) of the rectal diazepam group (percentage difference 29%; 95% CI, 16–41). For all episodes, median time after treatment until the seizure stopped was 8 minutes (interquartile range [IQR], 5 to 20 minutes) for buccal midazolam and 15 minutes (IQR 5 to 31 minutes) for rectal diazepam (P=.01; hazard ratio 0.7; 95% CI, 0.5–0.9). For all episodes, more children had stopped seizing within 10 minutes after receiving buccal midazolam (71 of 109, 65%) compared to rectal diazepam (45 of 110, 41%; P<.001). Seizure recurrence within the first hour was less likely for those given buccal midazolam (14% vs 33%; P=.02). New-onset versus established seizure disorder and presence or absence of fever did not affect results. Overall, buccal midazolam was found to be more effective than rectal diazepam (P<.001; odds ratio, 4.1; 95% CI, 2.2–7.6). There were 12 episodes of respiratory depression: 5 after midazolam and 7 after diazepam. There were 5 intubations: 2 after midazolam and 3 after diazepam. The authors conclude that buccal midazolam is just as safe and more effective than rectal diazepam for treatment of children with seizure in an ED setting.
Dr. Dubik has disclosed no financial relationships relevant to this commentary.
This study found buccal midazolam superior to rectal diazepam for the treatment of seizures. Midazolam had a quicker onset and a longer duration with no greater risk of respiratory depression. These findings confirm the results of a previous trial with...